Advertisement

Diagnosis and Characterization of Brain Tumors: MR Spectroscopic Imaging

  • Peter B. Barker
Chapter

Abstract

In vivo proton magnetic resonance spectroscopy (MRS) was first demonstrated to be feasible in vivo in the human brain in the mid-1980s [1], and the first example of it being applied to human brain tumors following soon after in 1989 [2]. It was already apparent from this paper that brain tumors had greatly different metabolite profiles compared to normal tissue, and that differences in spectra may exist between different brain lesions of different pathologies. Since that time, there has been steady progress in the use of MRS and the related technique of magnetic resonance spectroscopic imaging (MRSI) for the clinical evaluation of human brain tumors [3].

Keywords

Magnetic Resonance Spectroscopy Human Brain Tumor Chemical Shift Imaging Magnetic Resonance Spectroscopic Imaging Gliomatosis Cerebri 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Frahm J. Localized Proton Spectroscopy using stimulated echoes. J Magn Reson. 1987;72:502–8.Google Scholar
  2. 2.
    Bruhn H, Frahm J, Gyngell ML, et al. Noninvasive differentiation of tumors with use of localized H-1 MR spectroscopy in vivo: initial experience in patients with cerebral tumors. Radiology. 1989;172:541–8.Google Scholar
  3. 3.
    Barker PB, Lin DD. In vivo proton MR spectroscopy of the human brain. Prog NMR Spect. 2006;49:99–128.Google Scholar
  4. 4.
    Gupta RK, Cloughesy TF, Sinha U, et al. Relationships between choline magnetic resonance spectroscopy, apparent diffusion coefficient and quantitative histopathology in human glioma. J Neurooncol. 2000;50:215–26.Google Scholar
  5. 5.
    Aboagye EO, Bhujwalla ZM. Malignant transformation alters membrane choline phospholipid metabolism of human mammary epithelial cells. Cancer Res. 1999;59:80–4.Google Scholar
  6. 6.
    Brand A, Richter-Landsberg C, Leibfritz D. Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci. 1993;15:289–98.Google Scholar
  7. 7.
    Castillo M, Smith JK, Kwock L. Correlation of myo-inositol levels and grading of cerebral astrocytomas. AJNR Am J Neuroradiol. 2000;21:1645–9.Google Scholar
  8. 8.
    Demir MK, Iplikcioglu AC, Dincer A, Arslan M, Sav A. Single voxel proton MR spectroscopy findings of typical and atypical intracranial meningiomas. Eur J Radiol. 2006;60:48–55.Google Scholar
  9. 9.
    Arnold DL, Shoubridge EA, Villemure JG, Feindel W. Proton and phosphorus magnetic resonance spectroscopy of human astrocytomas in vivo. Preliminary observations on tumor grading. NMR Biomed. 1990;3:184–9.Google Scholar
  10. 10.
    Rock JP, Hearshen D, Scarpace L, et al. Correlations between magnetic resonance spectroscopy and image-guided histopathology, with special attention to radiation necrosis. Neurosurgery. 2002;51:912–9. discussion 919–920.Google Scholar
  11. 11.
    Tkac I, Andersen P, Adriany G, Merkle H, Ugurbil K, Gruetter R. In vivo 1H NMR spectroscopy of the human brain at 7 T. Magn Reson Med. 2001;46:451–6.Google Scholar
  12. 12.
    de Groot J, Sontheimer H. Glutamate and the biology of gliomas. Glia. 2011;59:1181–9.Google Scholar
  13. 13.
    Sontheimer H. Glutamate and tumor-associated epilepsy. Oncotarget. 2011;2:823–4.Google Scholar
  14. 14.
    Grossman SA, Ye X, Chamberlain M, et al. Talampanel with standard radiation and temozolomide in patients with newly diagnosed glioblastoma: a multicenter phase II trial. J Clin Oncol. 2009;27:4155–61.Google Scholar
  15. 15.
    Medina MA, Sanchez-Jimenez F, Marquez J, Rodriguez Quesada A, Nunez de Castro I. Relevance of glutamine metabolism to tumor cell growth. Mol cell biochem. 1992;113:1–15.Google Scholar
  16. 16.
    DeBerardinis RJ, Cheng T. Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene. 2010;29:313–24.Google Scholar
  17. 17.
    Yeung DK, Chan Y, Leung S, Poon PM, Pang C. Detection of an intense resonance at 2.4 ppm in 1H MR spectra of patients with severe late-delayed, radiation-induced brain injuries. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine/Society of. Magn Reson Med. 2001;45:994–1000.Google Scholar
  18. 18.
    Remy C, Grand S, Lai ES, et al. 1H MRS of human brain abscesses in vivo and in vitro. Magn Reson Med. 1995;34:508–14.Google Scholar
  19. 19.
    Bluml S, Panigrahy A, Laskov M, et al. Elevated citrate in pediatric astrocytomas with malignant progression. Neuro-Oncology. 2011;13:1107–17.Google Scholar
  20. 20.
    Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009;462:739–44.Google Scholar
  21. 21.
    Choi C, Ganji SK, DeBerardinis RJ, et al. 2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas. Nat Med. 2012;18:624–9.Google Scholar
  22. 22.
    Howe FA, Barton SJ, Cudlip SA, et al. Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy. Magn Reson Med. 2003;49:223–32.Google Scholar
  23. 23.
    Hourani R, Horska A, Albayram S, et al. Proton magnetic resonance spectroscopic imaging to differentiate between nonneoplastic lesions and brain tumors in children. Journal of magnetic resonance imaging : JMRI. 2006;23:99–107.Google Scholar
  24. 24.
    Graves EE, Nelson SJ, Vigneron DB, et al. Serial proton MR spectroscopic imaging of recurrent malignant gliomas after gamma knife radiosurgery. AJNR Am J Neuroradiol. 2001;22:613–24.Google Scholar
  25. 25.
    McKnight TR, von dem Bussche MH, Vigneron DB, et al. Histopathological validation of a three-dimensional magnetic resonance spectroscopy index as a predictor of tumor presence. J Neurosurg. 2002;97:794–802.Google Scholar
  26. 26.
    Nelson SJ. Multivoxel magnetic resonance spectroscopy of brain tumors. Mol Cancer Ther. 2003;2:497–507.Google Scholar
  27. 27.
    Nelson SJ, Graves E, Pirzkall A, et al. In vivo molecular imaging for planning radiation therapy of gliomas: an application of 1H MRSI. J Magn Reson Imaging. 2002;16:464–76.Google Scholar
  28. 28.
    Scheenen TW, Klomp DW, Wijnen JP, Heerschap A. Short echo time 1H-MRSI of the human brain at 3T with minimal chemical shift displacement errors using adiabatic refocusing pulses. Magn Reson Med. 2008;59:1–6.Google Scholar
  29. 29.
    Oz G, Tkac I. Short-echo, single-shot, full-intensity proton magnetic resonance spectroscopy for neurochemical profiling at 4 T: validation in the cerebellum and brainstem. Magn Reson Med. 2011;65:901–10.Google Scholar
  30. 30.
    Mlynarik V, Gambarota G, Frenkel H, Gruetter R. Localized short-echo-time proton MR spectroscopy with full signal-intensity acquisition. Magn Reson Med. 2006;56:965–70.Google Scholar
  31. 31.
    Haase A, Frahm J, Hanicke W, Matthei D. 1H NMR chemical shift selective imaging. Phys Med Biol. 1985;30:341–4.Google Scholar
  32. 32.
    Tkac I, Starcuk Z, Choi IY, Gruetter R. In vivo 1H NMR spectroscopy of rat brain at 1 ms echo time. Magn Reson Med. 1999;41:649–56.Google Scholar
  33. 33.
    Brown TR, Kincaid BM, Ugurbil K. NMR chemical shift imaging in three dimensions. Proc Natl Acad Sci U S A. 1982;79:3523–6.Google Scholar
  34. 34.
    Moonen CTW, Sobering G, van Zijl PCM, Gillen J, von Kienlin M, Bizzi A. Proton spectroscopic imaging of human brain. J Magn Reson. 1992;98:556–75.Google Scholar
  35. 35.
    Vigneron D, Bollen A, McDermott M, et al. Three-dimensional magnetic resonance spectroscopic imaging of histologically confirmed brain tumors. Magn Reson Imaging. 2001;19:89–101.Google Scholar
  36. 36.
    Duyn JH, Gillen J, Sobering G, van Zijl PC, Moonen CT. Multisection proton MR spectroscopic imaging of the brain. Radiology. 1993;188:277–82.Google Scholar
  37. 37.
    Ebel A, Soher BJ, Maudsley AA. Assessment of 3D proton MR echo-planar spectroscopic imaging using automated spectral analysis. Magn Reson Med. 2001;46:1072–8.Google Scholar
  38. 38.
    Duyn JH, Moonen CT. Fast proton spectroscopic imaging of human brain using multiple spin-echoes. Magn Reson Med. 1993;30:409–14.Google Scholar
  39. 39.
    Dydak U, Weiger M, Pruessmann KP, Meier D, Boesiger P. Sensitivity-encoded spectroscopic imaging. Magn Reson Med. 2001;46:713–22.Google Scholar
  40. 40.
    Bonekamp D, Smith MA, Zhu H, Barker PB. Quantitative SENSE-MRSI of the human brain. Magn reson imaging. 2010;28:305–13.Google Scholar
  41. 41.
    Banerjee S, Ozturk-Isik E, Nelson SJ, Majumdar S. Elliptical magnetic resonance spectroscopic imaging with GRAPPA for imaging brain tumors at 3 T. Magn reson imaging. 2009;27:1319–25.Google Scholar
  42. 42.
    Banerjee S, Ozturk-Isik E, Nelson SJ, Majumdar S. Fast magnetic resonance spectroscopic imaging at 3 Tesla using autocalibrating parallel technique. Conference proceedings : Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Conference 2006;1:1866–1869Google Scholar
  43. 43.
    Posse S, Tedeschi G, Risinger R, Ogg R, Le Bihan D. High speed 1H spectroscopic imaging in human brain by echo planar spatial-spectral encoding. Magn Reson Med. 1995;33:34–40.Google Scholar
  44. 44.
    Puts NA, Edden RA. In vivo magnetic resonance spectroscopy of GABA: a methodological review. Prog Nucl Magn Reson Spectrosc. 2012;60:29–41.Google Scholar
  45. 45.
    Mescher M, Merkle H, Kirsch J, Garwood M, Gruetter R. Simultaneous in vivo spectral editing and water suppression. NMR Biomed. 1998;11:266–72.Google Scholar
  46. 46.
    Provencher SW. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med. 1993;30:672–9.Google Scholar
  47. 47.
    Rabinov JD, Lee PL, Barker FG, et al. In vivo 3-T MR spectroscopy in the distinction of recurrent glioma versus radiation effects: initial experience. Radiology. 2002;225:871–9.Google Scholar
  48. 48.
    Gill SS, Thomas DG, Van Bruggen N, et al. Proton MR spectroscopy of intracranial tumours: in vivo and in vitro studies. J Comput Assist Tomogr. 1990;14:497–504.Google Scholar
  49. 49.
    Preul MC, Leblanc R, Caramanos Z, Kasrai R, Narayanan S, Arnold DL. Magnetic resonance spectroscopy guided brain tumor resection: differentiation between recurrent glioma and radiation change in two diagnostically difficult cases. Can J Neurol Sci. 1998;25:13–22.Google Scholar
  50. 50.
    Ricci PE, Pitt A, Keller PJ, Coons SW, Heiserman JE. Effect of voxel position on single-voxel MR spectroscopy findings. AJNR Am J neuroradiol. 2000;21:367–74.Google Scholar
  51. 51.
    Senft C, Hattingen E, Pilatus U, et al. Diagnostic value of proton magnetic resonance spectroscopy in the noninvasive grading of solid gliomas: comparison of maximum and mean choline values. Neurosurgery. 2009;65:908–13. discussion 913.Google Scholar
  52. 52.
    Chawla S, Wang S, Wolf RL, et al. Arterial spin-labeling and MR spectroscopy in the differentiation of gliomas. AJNR Am J Neuroradiol. 2007;28:1683–9.Google Scholar
  53. 53.
    Hwang JH, Egnaczyk GF, Ballard E, Dunn RS, Holland SK, Ball Jr WS. Proton MR spectroscopic characteristics of pediatric pilocytic astrocytomas. AJNR Am J Neuroradiol. 1998;19:535–40.Google Scholar
  54. 54.
    Panigrahy A, Krieger MD, Gonzalez-Gomez I, et al. Quantitative short echo time 1H-MR spectroscopy of untreated pediatric brain tumors: preoperative diagnosis and characterization. AJNR Am J Neuroradiol. 2006;27:560–72.Google Scholar
  55. 55.
    Fulham MJ, Bizzi A, Dietz MJ, et al. Mapping of brain tumor metabolites with proton MR spectroscopic imaging: clinical relevance. Radiology. 1992;185:675–86.Google Scholar
  56. 56.
    Tate AR, Griffiths JR, Martinez-Perez I, et al. Towards a method for automated classification of 1H MRS spectra from brain tumours. NMR Biomed. 1998;11:177–91.Google Scholar
  57. 57.
    Tate AR, Majos C, Moreno A, Howe FA, Griffiths JR, Arus C. Automated classification of short echo time in in vivo 1H brain tumor spectra: a multicenter study. Magn reson Med. 2003;49:29–36.Google Scholar
  58. 58.
    Wright AJ, Fellows G, Byrnes TJ, et al. Pattern recognition of MRSI data shows regions of glioma growth that agree with DTI markers of brain tumor infiltration. Magn Reson Med. 2009;62:1646–51.Google Scholar
  59. 59.
    Preul MC, Caramanos Z, Collins DL, et al. Accurate, noninvasive diagnosis of human brain tumors by using proton magnetic resonance spectroscopy. Nat Med. 1996;2:323–5.Google Scholar
  60. 60.
    De Edelenyi FS, Rubin C, Esteve F, et al. A new approach for analyzing proton magnetic resonance spectroscopic images of brain tumors: nosologic images. Nat Med. 2000;6:1287–9.Google Scholar
  61. 61.
    Fan G, Sun B, Wu Z, Guo Q, Guo Y. In vivo single-voxel proton MR spectroscopy in the differentiation of high-grade gliomas and solitary metastases. Clin Radiol. 2004;59:77–85.Google Scholar
  62. 62.
    Chiang IC, Kuo YT, Lu CY, et al. Distinction between high-grade gliomas and solitary metastases using peritumoral 3-T magnetic resonance spectroscopy, diffusion, and perfusion imagings. Neuroradiology. 2004;46:619–27.Google Scholar
  63. 63.
    Ishimaru H, Morikawa M, Iwanaga S, Kaminogo M, Ochi M, Hayashi K. Differentiation between high-grade glioma and metastatic brain tumor using single-voxel proton MR spectroscopy. Eur Radiol. 2001;11:1784–91.Google Scholar
  64. 64.
    Saindane AM, Cha S, Law M, Xue X, Knopp EA, Zagzag D. Proton MR spectroscopy of tumefactive demyelinating lesions. AJNR Am J Neuroradiol. 2002;23:1378–86.Google Scholar
  65. 65.
    Poptani H, Kaartinen J, Gupta RK, Niemitz M, Hiltunen Y, Kauppinen RA. Diagnostic assessment of brain tumours and non-neoplastic brain disorders in vivo using proton nuclear magnetic resonance spectroscopy and artificial neural networks. J Cancer Res Clin Oncol. 1999;125:343–9.Google Scholar
  66. 66.
    Poptani H, Gupta RK, Roy R, Pandey R, Jain VK, Chhabra DK. Characterization of intracranial mass lesions with in vivo proton MR spectroscopy. AJNR Am J Neuroradiol. 1995;16:1593–603.Google Scholar
  67. 67.
    Rand SD, Prost R, Haughton V, et al. Accuracy of single-voxel proton MR spectroscopy in distinguishing neoplastic from nonneoplastic brain lesions. AJNR Am J Neuroradiol. 1997;18:1695–704.Google Scholar
  68. 68.
    Butzen J, Prost R, Chetty V, et al. Discrimination between neoplastic and nonneoplastic brain lesions by use of proton MR spectroscopy: the limits of accuracy with a logistic regression model. AJNR Am J Neuroradiol. 2000;21:1213–9.Google Scholar
  69. 69.
    Moller-Hartmann W, Herminghaus S, Krings T, et al. Clinical application of proton magnetic resonance spectroscopy in the diagnosis of intracranial mass lesions. Neuroradiology. 2002;44:371–81.Google Scholar
  70. 70.
    De Stefano N, Caramanos Z, Preul MC, Francis G, Antel JP, Arnold DL. In vivo differentiation of astrocytic brain tumors and isolated demyelinating lesions of the type seen in multiple sclerosis using 1H magnetic resonance spectroscopic imaging. Ann Neurol. 1998;44:273–8.Google Scholar
  71. 71.
    Venkatesh SK, Gupta RK, Pal L, Husain N, Husain M. Spectroscopic increase in choline signal is a nonspecific marker for differentiation of infective/inflammatory from neoplastic lesions of the brain. J Magn Reson Imaging. 2001;14:8–15.Google Scholar
  72. 72.
    Vuori K, Kankaanranta L, Hakkinen AM, et al. Low-grade gliomas and focal cortical developmental malformations: differentiation with proton MR spectroscopy. Radiology. 2004;230:703–8.Google Scholar
  73. 73.
    Hourani R, Brant LJ, Rizk T, Weingart JD, Barker PB, Horska A. Can proton MR spectroscopic and perfusion imaging differentiate between neoplastic and nonneoplastic brain lesions in adults? AJNR Am J Neuroradiol. 2008;29:366–72.Google Scholar
  74. 74.
    Majos C, Aguilera C, Alonso J, et al. Proton MR spectroscopy improves discrimination between tumor and pseudotumoral lesion in solid brain masses. AJNR Am J Neuroradiol. 2009;30:544–51.Google Scholar
  75. 75.
    Al-Okaili RN, Krejza J, Wang S, Woo JH, Melhem ER. Advanced MR imaging techniques in the diagnosis of intraaxial brain tumors in adults. Radiographics. 2006;26 Suppl 1:S173–89.Google Scholar
  76. 76.
    Al-Okaili RN, Krejza J, Woo JH, et al. Intraaxial brain masses: MR imaging-based diagnostic strategy–initial experience. Radiology. 2007;243:539–50.Google Scholar
  77. 77.
    Garg M, Gupta RK. Spectroscopy in intracranial infection. In: Gillard J, Waldman A, Barker PB, editors. Clinical MR Neuroimaging: Diffusion, Perfusion and Spectroscopy. Cambridge, UK: Cambridge University Press; 2004. p. 380–406.Google Scholar
  78. 78.
    Saraswathy S, Crawford FW, Lamborn KR, et al. Evaluation of MR markers that predict survival in patients with newly diagnosed GBM prior to adjuvant therapy. J Neurooncol. 2009;91:69–81.Google Scholar
  79. 79.
    Crawford FW, Khayal IS, McGue C, et al. Relationship of pre-surgery metabolic and physiological MR imaging parameters to survival for patients with untreated GBM. J Neurooncol. 2009;91:337–51.Google Scholar
  80. 80.
    Chan AA, Lau A, Pirzkall A, et al. Proton magnetic resonance spectroscopy imaging in the evaluation of patients undergoing gamma knife surgery for Grade IV glioma. J Neurosurg. 2004;101:467–75.Google Scholar
  81. 81.
    Guzman-de-Villoria JA, Sanchez-Gonzalez J, Munoz L, et al. 1H MR spectroscopy in the assessment of gliomatosis cerebri. AJR Am J Roentgenol. 2007;188:710–4.Google Scholar
  82. 82.
    Kuznetsov YE, Caramanos Z, Antel SB, et al. Proton magnetic resonance spectroscopic imaging can predict length of survival in patients with supratentorial gliomas. Neurosurgery. 2003;53:565–74. discussion 574–566.Google Scholar
  83. 83.
    Sjobakk TE, Johansen R, Bathen TF, et al. Metabolic profiling of human brain metastases using in vivo proton MR spectroscopy at 3T. BMC Cancer. 2007;7:141.Google Scholar
  84. 84.
    Raizer JJ, Koutcher JA, Abrey LE, et al. Proton magnetic resonance spectroscopy in immunocompetent patients with primary central nervous system lymphoma. J Neurooncol. 2005;71:173–80.Google Scholar
  85. 85.
    Hattingen E, Raab P, Franz K, et al. Prognostic value of choline and creatine in WHO grade II gliomas. Neuroradiology. 2008;50:759–67.Google Scholar
  86. 86.
    Marcus KJ, Astrakas LG, Zurakowski D, et al. Predicting survival of children with CNS tumors using proton magnetic resonance spectroscopic imaging biomarkers. Int J Oncol. 2007;30:651–7.Google Scholar
  87. 87.
    Warren KE, Frank JA, Black JL, et al. Proton magnetic resonance spectroscopic imaging in children with recurrent primary brain tumors. J Clin Oncol. 2000;18:1020–6.Google Scholar
  88. 88.
    Law M, Cha S, Knopp EA, Johnson G, Arnett J, Litt AW. High-grade gliomas and solitary metastases: differentiation by using perfusion and proton spectroscopic MR imaging. Radiology. 2002;222:715–21.Google Scholar
  89. 89.
    Einstein DB, Wessels B, Bangert B, et al. Phase II trial of radiosurgery to magnetic resonance spectroscopy-defined high-risk tumor volumes in patients with glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 2012;84:668–74.Google Scholar
  90. 90.
    Weber MA, Giesel FL, Stieltjes B. MRI for identification of progression in brain tumors: from morphology to function. Expert Rev Neurother. 2008;8:1507–25.Google Scholar
  91. 91.
    Hygino da Cruz Jr LC, Domingues RC, Gasparetto EL, Sorensen AG. Pseudoprogression and pseudoresponse: imaging challenges in the assessment of posttreatment glioma. AJNR Am J Neuroradiol. 2011;32:1978–85.Google Scholar
  92. 92.
    Brandsma D, Stalpers L, Taal W, Sminia P, van den Bent MJ. Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol. 2008;9:453–61.Google Scholar
  93. 93.
    Smith EA, Carlos RC, Junck LR, Tsien CI, Elias A, Sundgren PC. Developing a clinical decision model: MR spectroscopy to differentiate between recurrent tumor and radiation change in patients with new contrast-enhancing lesions. AJR Am J Roentgenol. 2009;192:W45–52.Google Scholar
  94. 94.
    Fink JR, Carr RB, Matsusue E, et al. Comparison of 3 Tesla proton MR spectroscopy, MR perfusion and MR diffusion for distinguishing glioma recurrence from posttreatment effects. J Magn reson imaging. 2012;35:56–63.Google Scholar
  95. 95.
    Prat R, Galeano I, Lucas A, et al. Relative value of magnetic resonance spectroscopy, magnetic resonance perfusion, and 2-(18F) fluoro-2-deoxy-D-glucose positron emission tomography for detection of recurrence or grade increase in gliomas. J Clin Neurosci. 2010;17:50–3.Google Scholar
  96. 96.
    Sundgren PC. MR spectroscopy in radiation injury. AJNR Am J Neuroradiol. 2009;30:1469–76.Google Scholar
  97. 97.
    Sundgren PC, Nagesh V, Elias A, et al. Metabolic alterations: a biomarker for radiation-induced normal brain injury-an MR spectroscopy study. J Magn reson imaging. 2009;29:291–7.Google Scholar
  98. 98.
    Esteve F, Rubin C, Grand S, Kolodie H, Le Bas JF. Transient metabolic changes observed with proton MR spectroscopy in normal human brain after radiation therapy. Int J Radiat Oncol Biol Phys. 1998;40:279–86.Google Scholar
  99. 99.
    Jeon JY, Kovanlikaya I, Boockvar JA, et al. Metabolic response of glioblastoma to superselective intra-arterial cerebral infusion of bevacizumab: a proton MR spectroscopic imaging study. AJNR Am J Neuroradiol. 2012;33:2095–102.Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of RadiologyJohns Hopkins University School of MedicineBaltimoreUSA

Personalised recommendations